Evidence map›Paper›PMID 33600495›Full record

ArticlePLoS pathogens2021

Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells.

Merryn Fraser, Weidong Jing, Stefan Bröer, Florian Kurth, Leif-Erik Sander, Kai Matuschewski, Alexander G Maier

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. The role of cholesterol in invasion and growth of malaria parasites.Frontiers in cellular and infection microbiology · 2022
    Review
  14. Article
  15. Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Merryn FraserResearch School of Biology, The Australian National University, Canberra, Australia.ORCID 0000-0002-9983-1474
Weidong JingResearch School of Biology, The Australian National University, Canberra, Australia.ORCID 0000-0002-6747-6076
Stefan BröerResearch School of Biology, The Australian National University, Canberra, Australia.ORCID 0000-0002-8040-1634
Florian KurthDepartment of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Germany.ORCID 0000-0002-3807-473X
Leif-Erik SanderDepartment of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Germany.ORCID 0000-0002-0476-9947
Kai MatuschewskiDepartment of Molecular Parasitology, Institute of Biology, Humboldt University, Berlin, Germany.ORCID 0000-0001-6147-8591
Alexander G MaierResearch School of Biology, The Australian National University, Canberra, Australia.ORCID 0000-0001-7369-1058
Australian National University · AUCharité - Universitätsmedizin Berlin · DEHumboldt-Universität zu Berlin · DEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human malaria parasite Plasmodium falciparum relies on lipids to survive; this makes its lipid metabolism an attractive drug target. The lipid phosphatidylserine (PS) is usually confined to the inner leaflet of the red blood cell membrane (RBC) bilayer; however, some studies suggest that infection with the intracellular parasite results in the presence of this lipid in the RBC membrane outer leaflet, where it could act as a recognition signal to phagocytes. Here, we used fluorescent lipid analogues and probes to investigate the enzymatic reactions responsible for maintaining asymmetry between membrane leaflets, and found that in parasitised RBCs the maintenance of membrane asymmetry was partly disrupted, and PS was increased in the outer leaflet. We examined the underlying causes for the differences between uninfected and infected RBCs using fluorescent dyes and probes, and found that calcium levels increased in the infected RBC cytoplasm, whereas membrane cholesterol was depleted from the erythrocyte plasma membrane. We explored the resulting effect of PS exposure on enhanced phagocytosis by monocytes, and show that infected RBCs must expend energy to limit phagocyte recognition, and provide experimental evidence that PS exposure contributes to phagocytic recognition of P. falciparum-infected RBCs. Together, these findings underscore the pivotal role for PS exposure on the surface of Plasmodium falciparum-infected erythrocytes for in vivo interactions with the host immune system, and provide a rationale for targeted antimalarial drug design.

Indexed as

PhagocytosisCalciumErythrocyte MembraneErythrocytesHumansMalaria, FalciparumMonocytesPhosphatidylserinesPlasmodium falciparumCalciumPhosphatidylserines

Identifiers

PMID33600495
PMCPMC7891792
OpenAlexW3130880641

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.